Mutant microbes could keep you young

Swallow some mutant E. Coli to slow ageing? It works, at least if you’re the tiny roundworm Caenorhabditis elegans.

That’s the finding of a new study led by Meng Wang at Baylor College of Medicine in Houston.

“But I’m not a tiny roundworm,” I hear you say. True enough, but bear in mind that this inauspicious creature has been shedding light on the clockwork of the ageing machinery for the last 30 years. What’s true for worms has often turned out to be true for us.

The link between longevity and insulin signalling, for instance, was discovered here.  Since then, two diabetes drugs, metformin and acarbose, which tinker with the same pathways as insulin, have been found to extend the lifespan of some strains of mice and human trials are being planned.

More recently the microbiome, particularly the composition of gut bacteria, has been linked to human ageing.

To zero in on just how bacteria could influence ageing, Wang, a long-time student of longevity in C. elegans, turned to her trusty roundworm. It turns out to be an ideal creature to answer the question. Not only does it age conspicuously over a period of two weeks, from svelte slitherer to tubby, uncoordinated geriatric, it feeds on bacteria and houses them in its gut, as we do.

To test the effects of gut bacteria on longevity, the worms were reared in sterile conditions and then allowed to feast on one strain of E. Coli at a time. Overall 4000 strains were tested, each representing a mutation in one of the 4000 E. Coli genes

Twenty-nine of the mutants extended the worm’s lifespan, while 12 also had added benefits including protecting the worms from cancer and the build-up of amyloid-beta, a toxic protein linked to Alzheimer’s Disease in humans.

What were these helpful bacteria doing? It turned out most were releasing factors that tweaked pathways already known to influence aging: the insulin pathway or another called the TOR pathway which stimulates autophagy, a healthy recycling process that goes on inside cells.

However, one mutant that extended lifespan and protected against cancer and amyloid build-up did something entirely new: It overproduced a sugary substance called colanic acid. Feeding the worms colonic acid on its own also increased their lifespans. Feeding colanic acid to fruit flies also increased their lifespans.

So how does colanic acid do what it does? There are two hints. As Wang explains, E. Coli that are aggregating to form a potentially dangerous biofilm secrete the sticky sugar like a shield to protect themselves.  Colanic acid also activates mitochondria (the power factories inside cells), to produce corrosive chemicals known as reactive oxygen species (ROS). Long thought to be the agents of ageing, it now turns that ROS can also trigger anti-ageing responses.

So one possibility is that as bacteria form harmful biofilms and release colanic acid, mitochondria sound the alarm by releasing ROS, which in turn activate protective anti-ageing responses. “That’s our current hypothesis,” says Wang.

Given how other worm findings have translated to humans, Wang thinks this finding will travel the same route: “All the same genes exist in our microbiome.” Further research will take time, but the life-extension industry may well get ahead of it. Don’t be surprised if you start seeing ads blaring ‘ Colanic acid, anti-ageing wonder drug’.